Painful gynecomastia in a patient with malignant thymoma
Malign timomal› bir hastada a¤r›l› jinekomasti
Gamze Gököz DO⁄U,1Fatih TANRIVERD‹,2Mustafa D‹K‹L‹TAfi,1
Metin ÖZKAN,1Kürflat ÜNLÜH‹ZARCI,2Özlem ER1
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C o r re s p o n d e n c e (‹ l e t i fl i m): Gamze Gököz DO⁄U, M.D. Erciyes Üniversitesi T›p Fakültesi, Medikal Onkoloji Anabilim Dal›, Kayseri, Tu r k e y . Tel: +90 - 352 - 437 49 01 e -m a i l ( e -p o s t a): ggd2882@gmail.com
Erciyes Üniversitesi T›p Fakültesi, 1Medikal Onkoloji Anabilim Dal›, 2Endokrinoloji ve Metabolizma Hastal›klar› Anabilim Dal›
Türk Onkoloji Dergisi 2008;23(2):100-103
Jinekomasti, erkek memesinde anormal volüm artıflı ile ken-dini gösterir. Bu patolojik de¤ifliklik tek veya çift taraflı ola-bilir ve genellikle artmıfl östrojen/androjen oranıyla iliflkilidir. Jinekomasti pubertal ça¤da ve yafllılarda daha yaygındır. Ke-moterapi ile gonadal ve hormonal fonksiyonlar hasara u¤ra-yarak jinekomasti geliflebilir. Bu yazıda, iki tarafl› akut a¤rılı jinekomastili malign timoma tanısı olan 36 yaflındaki bir er-kek hasta bildirildi, bu konudaki literatür bilgisi özetlendi. Hastaya tamoksifen günde 20 mg olarak bafllandı. Yirmi gün sonra tamoksifenle jinekomastide tamamen gerileme gözlen-di. Literatür arafltırması yaptı¤ımızda malign timomada jine-komasti bildirimine rastlamadık.
Anahtar sözcükler: A¤r›l› jinekomasti; malign timoma; tamoksifen.
Gynecomastia is an abnormal increase in the volume of the male breast, characterized by a ten-der discoid enlargement 2-4 cm in diameter beneath the areola, with hypertrophy of the gland and the surrounding fatty tissue. This pathological change may occur unilaterally or bilaterally and is generally considered to be due to an increased estrogen/androgen ratio.
Gynecomastia is more common in pubertal ages and in older men. Chemotherapy may injure gonadal and hormonal functions and is associated with the development of gynecomastia.
CASE REPORT
A 36-year-old man with an anterior mediastinal mass and respiratory failure was admitted to our hospital 9 months ago. Debulking surgery was per-formed via median sternotomy. Histopathological diagnosis had revealed unresectable thymic cancer, and induction chemotherapy was administered
(cyclophosphamide 500 mg/m2, epirubicin 7 5
mg/m2, and cisplatin 75 mg/m2on day 1; and
pred-nisone 100 mg/per day on days 1-5). This cycle was repeated four times at three-week intervals. Surgery was not possible because of extensive
vas-Gynecomastia is an abnormal increase in the volume of the male breast. This pathological change may occur unilaterally or bilaterally and is generally considered to be due to an increased estrogen/androgen ratio. Gynecomastia is more common in pubertal ages and in older men. Chemotherapy may injure gonadal and hormonal functions and are associated with devel-opment of gynecomastia. In this case, a 36-year-old man who had bilateral acute painful gynecomastia associated with malig-nant thymoma is presented together with a review of the litera-ture. Tamoxifen 20 mg daily was started. Twenty days later, tamoxifen resulted in complete regression of gynecomastia. After an extensive literature search, we found that gynecomas-tia had not been previously documented in malignant thymoma.
cular invasion. He was treated with radiotherapy (total dose 6000 Gy in 30 fractions in six weeks). One month later, the patient presented with bilat-eral acute painful gynecomastia. Physical exami-nation showed slightly enlarged breasts (Fig. 1).
The patient presented with bilateral acute painful gynecomastia. On physical examination, he appeared well, and his vital signs were normal. The lungs were clear, heart sounds were normal, and the abdomen was soft, with no masses or ten-derness. The results of a complete blood count and the levels of electrolytes, calcium, creatinine, urea nitrogen, protein, albumin, globulin, and bilirubin were normal. There was no adenopathy, and tes-ticular examination was normal. Abdominal ultra-sonography (USG), testicular USG, and magnetic resonance imaging of the sella turcica were nor-mal. Follicle-stimulating hormone (FSH) 26.18 (1.4-18 mIU/ml) and luteinizing hormone (LH) 16.83 (1.5-9.3 mIU/ml) were high. Beta-human chorionic gonadotropin, testosterone, prolactin, dehydroepiandrosterone sulfate, alpha-fetopro-tein, insulin-like growth factor 1, thyroid function tests and cortisol level were normal. In view of progression in this patient, ifosfamide was given as second-line chemotherapy. Tamoxifen (TAM)
20 mg daily was started. Twenty days later, TAM resulted in complete regression of gynecomastia and there has been no recurrence in follow-up physical examinations.
D I S C U S S I O N
Gynecomastia is common, present in 30% to 50% of healthy men. Conditions associated with gynecomastia are shown in Table 1. Men with recent-onset gynecomastia or mastodynia need a more detailed evaluation, including selected labo-ratory tests, to search for an underlying cause. Treatment depends on the cause and may include observation, withdrawal of an offending drug, therapy of an underlying disease, administration of androgen or antiestrogen drugs, or plastic surgery. Most cases of gynecomastia result from an imbalance between estrogenic (stimulatory) and androgenic (inhibitory) effects on the breast. Drug-induced gynecomastia accounts for 20% to
25% of cases.[1] Some drugs can cause
gyneco-mastia through multiple mechanisms. For exam-ple, drugs mimicking or having estrogenic or antiandrogenic effects may also be associated
with development of gynecomastia.[2 - 4]Even with
detailed evaluation, there is no identifiable cause
Fig. 1. The patient presenting with bilateral gynecomastia.
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Türk Onkoloji Dergisi
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Second, the resulting increase in serum LH stimu-lates the aromatase enzyme in testicular Leydig cells to produce more estrogen. In addition, peripheral aromatization of the adrenal androgen androstenedione to estrogen remains unaffected.
Preliminary efficacy data from a retrospective chart review of patients with gynecomastia indi-cated that TAM was associated with reductions in
breast size and decreased pain.[5] TAM, in an
uncontrolled study, resulted in complete
regres-sion of gynecomastia in 70% of cases.[6]
in about 25% of cases. Causes may include exces-sive local production of estrogen due to increased aromatase activity, decreased estrogen degrada-tion, or changes in androgen or estrogen recep-t o r s.
Primary hypogonadism due to Leydig cell damage from any cause (e.g., mumps orchitis, trauma, cytotoxic chemotherapy, alkylating agents, vincristine, nitrosoureas, methotrexate) is commonly associated with gynecomastia. First, levels of total and free testosterone decrease.
Table 1 Causes of gynecomastia Physiological Pathological Neonatal Idiopathic Pubertal Drug-induced Aging
Increased serum estrogen Decreased testosterone synthesis Increased aromatization (peripherally or glandular) Primary gonadal failure, congenital
Sertoli cell tumors Anorchia
Sex cord tumors Klinefelter syndrome
Testicular germ cell tumors Hermaphroditism
Leydig cell tumors Hereditary defects in testosterone synthesis Adrenocortical tumors Primary gonadal failure, acquired
Hermaphroditism Viral orchitis
Obesity Castration
Hyperthyroidism Granulomatous disease (including leprosy)
Liver disease Testicular failure due to hypothalamic and/or pituitary disease Testicular feminization Androgen resistance due to androgen receptor defects Refeeding after starvation
Primary aromatase excess
Displacement of estrogen from SHBG Spironolactone
Ketoconazole Decreased estrogen metabolism
Cirrhosis (?) Exogenous sources
Topical estrogen creams and lotions Ectopic hCG production
Lung carcinoma Other
Choriocarcinoma Chronic renal failure
Liver carcinoma Chronic illness
Kidney carcinoma HIV
Gastric carcinoma Enhanced breast tissue sensitivity
Painful gynecomastia in a patient with malignant thymoma
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LH and FSH are secreted by adenocarcinoma and large cell carcinoma. However, to our knowl-edge, there is no case in the literature describing paraneoplastic gynecomastia with malignant thy-moma. It can be speculated that LH and FSH are secreted in malignant thymoma and that gyneco-mastia developed as a paraneoplastic entity.
R E F E R E N C E S
1. Braunstein GD. Gynecomastia. N Engl J Med 1993;328(7):490-5.
2. Carlson HE. Gynecomastia. N Engl J Med
1980;303(14):795-9.
3. Croce P, Montanari G, Zinzalini G, Iacona A. Gynecomastia. [Article in Italian] Minerva Med 1992;83(10):609-14. [Abstract]
4. Glass AR. Gynecomastia. Endocrinol Metab Clin North Am 1994;23(4):825-37.
5. Ting AC, Chow LW, Leung YF. Comparison of tamoxifen with danazol in the management of idio-pathic gynecomastia. Am Surg 2000;66(1):38-40. 6. Parker LN, Gray DR, Lai MK, Levin ER. Treatment of
gynecomastia with tamoxifen: a double-blind crossover study. Metabolism 1986;35(8):705-8.
